Abstract

We have developed new algorithms to model complex biological flows in integrated biodetection microdevice components. The proposed work is important because the design strategy for the next-generation Autonomous Pathogen Detection System at LLNL is the microfluidic-based Biobriefcase, being developed under the Chemical and Biological Countermeasures Program in the Homeland Security Organization. This miniaturization strategy introduces a new flow regime to systems where biological flow is already complex and not well understood. Also, design and fabrication of MEMS devices is time-consuming and costly due to the current trial-and-error approach. Furthermore, existing devices, in general, are not optimized. There are several MEMS CAD capabilities currently available, but their computational fluid dynamics modeling capabilities are rudimentary at best. Therefore, we proposed a collaboration to develop computational tools at LLNL which will (1) provide critical understanding of the fundamental flow physics involved in bioMEMS devices, (2) shorten the design and fabrication process, and thus reduce costs, (3) optimize current prototypes and (4) provide a prediction capability for the design of new, more advanced microfluidic systems. Computational expertise was provided by Comp-CASC and UC Davis-DAS. The simulation work was supported by key experiments for guidance and validation at UC Berkeley-BioE.

@article{osti_877830,
title = {FY05 LDRD Final Report A Computational Design Tool for Microdevices and Components in Pathogen Detection Systems},
author = {Trebotich, D},
abstractNote = {We have developed new algorithms to model complex biological flows in integrated biodetection microdevice components. The proposed work is important because the design strategy for the next-generation Autonomous Pathogen Detection System at LLNL is the microfluidic-based Biobriefcase, being developed under the Chemical and Biological Countermeasures Program in the Homeland Security Organization. This miniaturization strategy introduces a new flow regime to systems where biological flow is already complex and not well understood. Also, design and fabrication of MEMS devices is time-consuming and costly due to the current trial-and-error approach. Furthermore, existing devices, in general, are not optimized. There are several MEMS CAD capabilities currently available, but their computational fluid dynamics modeling capabilities are rudimentary at best. Therefore, we proposed a collaboration to develop computational tools at LLNL which will (1) provide critical understanding of the fundamental flow physics involved in bioMEMS devices, (2) shorten the design and fabrication process, and thus reduce costs, (3) optimize current prototypes and (4) provide a prediction capability for the design of new, more advanced microfluidic systems. Computational expertise was provided by Comp-CASC and UC Davis-DAS. The simulation work was supported by key experiments for guidance and validation at UC Berkeley-BioE.},
doi = {10.2172/877830},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Feb 07 00:00:00 EST 2006},
month = {Tue Feb 07 00:00:00 EST 2006}
}

We have demonstrated that it is possible to enhance current radiation detection capability by manipulating the materials at the nano level. Fabrication of three-dimensional (3-D) nanomaterial composite for radiation detection has great potential benefits over current semiconductor- and scintillation-based technologies because of the precise control of material-radiation interaction and modulation of signal output. It is also a significant leap beyond current 2-D nanotechnology. Moreover, since we are building the materials using a combination of top-down and bottom-up approaches, this strategy to make radiation detection materials can provide significant improvement to radiation-detection technologies, which are currently based on difficult-to-control bulk crystalmore » growth techniques. We are applying this strategy to tackle two important areas in radiation detection: gamma-rays and neutrons. In gamma-ray detection, our first goal is to employ nanomaterials in the form of quantum-dot-based mixed matrices or nanoporous semiconductors to achieve scintillation output several times over that from NaI(Tl) crystals. In neutron detection, we are constructing a 3-D structure using a doped nanowire ''forest'' supported by a boron matrix and evaluating the detection efficiency of different device geometry with simulation.« less

The detection of the unconventional delivery of a nuclear weapon or the illicit transport of fissile materials is one of the most crucial, and difficult, challenges facing us today in national security. A wide array of radiation detectors are now being deployed domestically and internationally to address this problem. This initial deployment will be followed by radiation detection systems, composed of intelligent, networked devices intended to supplement the choke-point perimeter systems with more comprehensive broad-area, or regional coverage. Cataloging and fusing the data from these new detection systems will clearly be one of the most significant challenges in radiation-based securitymore » systems. We present here our results from our first 6 months of effort on this project. We anticipate the work will continue as part of the Predictive Knowledge System Strategic Initiative.« less

In the event of a nuclear or radiological accident or terrorist event, it is important to identify individuals that can benefit from prompt medical care and to reassure those that do not need it. Achieving these goals will maximize the ability to manage the medical consequences of radiation exposure that unfold over a period of hours, days, weeks, years, depending on dose. Medical interventions that reduce near term morbidity and mortality from high but non-lethal exposures require advanced medical support and must be focused on those in need as soon as possible. There are two traditional approaches to radiation dosimetry,more » physical and biological. Each as currently practiced has strengths and limitations. Physical dosimetry for radiation exposure is routine for selected sites and for individual nuclear workers in certain industries, medical centers and research institutions. No monitoring of individuals in the general population is currently performed. When physical dosimetry is available at the time of an accident/event or soon thereafter, it can provide valuable information in support of accident/event triage. Lack of data for most individuals is a major limitation, as differences in exposure can be significant due to shielding, atmospherics, etc. A smaller issue in terms of number of people affected is that the same dose may have more or less biological effect on subsets of the population. Biological dosimetry is the estimation of exposure based on physiological or cellular alterations induced in an individual by radiation. The best established and precise biodosimetric methods are measurement of the decline of blood cells over time and measurement of the frequency of chromosome aberrations. In accidents or events affecting small numbers of people, it is practical to allocate the resources and time (days of clinical follow-up or specialists laboratory time) to conduct these studies. However, if large numbers of people have been exposed, or fear they may have been, these methods are not suitable. The best current option for triage radiation biodosimetry is self-report of time to onset of emesis after the event, a biomarker that is subject to many false positives. The premise of this project is that greatly improved radiation dosimetry can be achieved by research and development directed toward detection of molecular changes induced by radiation in cells or other biological materials. Basic research on the responses of cells to radiation at the molecular level, particularly of message RNA and proteins, has identified biomolecules whose levels increase (or decrease) as part of cellular responses to radiation. Concerted efforts to identify markers useful for triage and clinical applications have not been reported as yet. Such studies would scan responses over a broad range of doses, below, at and above the threshold of clinical significance in the first weeks after exposure, and would collect global proteome and/or transcriptome information on all tissue samples accessible to either first responders or clinicians. For triage, the goal is to identify those needing medical treatment. Treatment will be guided by refined dosimetry. Achieving this goal entails determining whether radiation exposure was below or above the threshold of concern, using one sample collected within days of an event, with simple devices that first responders either use or distribute for self-testing. For the clinic, better resolution of dose and tissue damage is needed to determine the nature and time sensitivity of therapy, but multiple sampling times may be acceptable and clinical staff and equipment can be utilized. Two complementary areas of research and development are needed once candidate biomarkers are identified, validation of the biomarker responses and validation of devices/instrumentation for detection of responses. Validation of biomarkers per se is confirmation that the dose, time, and tissue specific responses meet the reporting requirements in a high proportion of the population, and that variation among nonexposed people due to age, life-style factors, common medical conditions, variables that are not radiation related, do not lead to unacceptable frequencies of false negatives or false positives. Validation of detection requires testing of devices/instruments for accuracy and reproducibility of results with the intended reagents, sampling protocols, and users. Different technologies, each with intrinsic virtues and liabilities, will be appropriate for RNA and protein biomarkers. Fortunately, device and instrumentation development for other clinical applications is a major industry. Hence the major challenges for radiation biodosimetry are identification of potential radiation exposure biomarkers and development of model systems that enable validation of responses of biomarkers and detection systems.« less

In order to shed light on the intriguing, and not yet fully understood fcc-isostructural {gamma} {yields} {alpha} transition in cerium, we have begun an experimental program aimed at the determination of the pressure evolution of the transverse acoustic (TA) and longitudinal acoustic (LA) phonon dispersions up to and above the transition. {gamma}-Ce Crystals of 60-80 mm diameter and 20 mm thickness were prepared from a large ingot, obtained from Ames Lab, using laser cutting, micro-mechanical and chemical polishing techniques. Three samples with a surface normal approximately oriented along the [110] direction were loaded into diamond anvil cells (DAC), using neonmore » as a pressure transmitting medium. The crystalline quality was checked by rocking curve scans and typical values obtained ranged between one and two degrees. Only a slight degradation in the sample quality was observed when the pressure was increased to reach the {alpha}-phase, and data could be therefore recorded in this phase as well. The spectrometer was operated at 17794 eV in Kirkpatrick-Baez focusing geometry, providing an energy resolution of 3 meV and a focal spot size at the sample position of 30 x 60 mm{sup 2} (horizontal x vertical, FWHM). Eight to ten IXS spectra were typically recorded per phonon branch. Figure 1 reports the pressure dependence of the LA[100] branch in the {gamma}-phase for pressures of 1, 4 and 6 kbar, together with previous inelastic neutron scattering (INS) results [1] at ambient pressure. A clear decrease of the phonon energies with increasing pressure is observed for 1 and 4 kbar, whereas the phonon energies increase again at 6 kbar, still well within the stability field of the {gamma}-phase. Figure 2 reports the LA dispersion along all three main symmetry directions at 6 kbar ({gamma}-phase) and 8 kbar ({alpha}-phase), together with the INS results at ambient conditions. Besides the already discussed unusual behavior along the [100] direction, the pressure evolution of the two other longitudinal branches in the {gamma}-phase is quite different. The LA [110] branch displays a downward bending near the zone boundary (ZB), whereas the phonon energies at low reduced momentum transfer remain close to the ones at room pressure. In contrast to this, the LA [111] branch does not display any pressure dependence. The LA phonon energies in the {alpha}-phase at 8 kbar are systematically higher than the corresponding lower pressure phonon energies, consistent with the higher density of the {alpha}-phase and the expected larger elastic constants. We note, however, substantial changes in the lattice dynamics along the [110] direction. While the phonons between {zeta} = 0.4 and 0.6 show a large energy increase with pressure, the phonon energy decreases at the zone boundary, thus leading to a pronounced overbending of the branch. The shape of the LA phonon branches in the {alpha}-phase are close to those measured in thorium at ambient conditions [2] while the {gamma}-phase phonon dispersion resembles fcc metastable lanthanum [3]. This behavior might be a signature of substantial changes in the Fermi surface topology, leading to significant changes in the electron-phonon coupling mechanism. A Born-von Karman fit to the phonon dispersion is currently being performed in order to quantify the changes in the force constant matrix.« less

We summarize the observations of unusual optical properties of shocked liquid deuterium (D{sub 2}) that led to proposing spectroscopic measurements. The apparatus built for the measurements is briefly described, along with some representative results in a test material. Unfortunately, spectroscopic measurements were not performed in shocked D{sub 2} during the course of the project. Some reasons are noted.